HBsAg-Serum Protein Complexes Stimulate Immune T Lymphocytes More Efficiently Than Do Pure HBsAg

Abstract

HBsAg from plasma of chronic hepatitis B carriers was purified by affinity chromatography using a mouse monoclonal antibody specific for HBsAg. Elution with buffer at two different pH values separated HBsAg into two fractions: one contained high amounts of immune complexes associated with HBsAg; the other contained larger quantities of the HBsAg polypeptides P24 and GP27 and only small amounts of immunoglobulin. When compared for effects on stimulating the proliferative response of freshly isolated lymphocytes and an HBsAg-specific T cell clone, the HBsAg fraction containing a high proportion of immunoglobulin was much more potent than HBsAg with low amounts of immunoglobulins or pure HBsAg, which was isolated from the culture supernatant of the human hepatoma cell line (PLC/PRF/5). The plasma-derived HBsAg with low amounts of complexed immunoglobulins became more immunogenic in the presence of an anti-HBsAg monoclonal IgG. The present results, combined with earlier findings, suggest that HBsAg associated with immune complexes is a more potent stimulator of T cells than purer HBsAg preparations due to an increase in the efficiency of monocytes to capture the antigen through binding to immune complexes for subsequent processing and presentation of the antigen. These observations could be of relevance for the preparation of effective hepatitis B vaccines from recombinant DNA and peptide synthesis technologies.

Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

“…HBsAg/anti-HBV ICs significantly increased the uptake of the immunocomplexed HBsAg antigen, and augmented the in vitro proliferation of virus-specific T cells and their production of interferon (IFN)-γ. 55 Moreover, DCs from HBV-infected patients incubated with HBsAg/anti-HBV ICs showed higher expression of major histocompatibility complex (MHC)-II molecules and higher production of interleukin (IL)-12. IC-loaded DCs also enhanced production of IL-2 and IFN-γ by co-cultured T cells.…”

Antibody-Mediated Immunomodulation: a Strategy To Improve Host Responses against Microbial Antigens

“…This finding may be of direct clinical applicability, considering the relatively high percentage of individuals who do not seroconvert following immunzation with HBsAg alone (22) in that additional target epitopes would be available and potentially recognizable by the nonresponding population. IC of HBsAg and MAbs have been reported to stimulate proliferation of immune T lymphocytes more efficiently than did antigen alone (31), and promising therapeutic efficacy of an IC vaccine in the treatment of chronic hepatitis B patients has been reported (125,130). MAbs administered as part of IC have also been demonstrated to influence the humoral immune response against the P1 surface adhesin of the dental pathogen Streptococcus mutans (18,87,99,100).…”

CD32 Ligation Promotes the Activation of CD4+ T Cells

“…High levels of ICs are found in chronic viral infections and autoimmune diseases ( 22 ). Moreover, a large body of evidence suggest that ICs play a key role not only in the induction of tissue injury, but also in the promotion of T cell responses ( 23 – 28 ). The mechanisms underlying the ability of ICs to promote the stimulation of T cells have not been clearly defined yet.…”